Comparison of two PET radioligands, [11C]FPEB and [11C]SP203, for quantification of metabotropic glutamate receptor 5 in human brain

J Cereb Blood Flow Metab. 2017 Jul;37(7):2458-2470. doi: 10.1177/0271678X16668891. Epub 2016 Jan 1.

Abstract

Of the two 18F-labeled PET ligands currently available to image metabotropic glutamate receptor 5 (mGluR5), [18F]FPEB is reportedly superior because [18F]SP203 undergoes glutathionlyation, generating [18F]-fluoride ion that accumulates in brain and skull. To allow multiple PET studies on the same day with lower radiation exposure, we prepared [11C]FPEB and [11C]SP203 from [11C]hydrogen cyanide and compared their abilities to accurately quantify mGluR5 in human brain, especially as regards radiometabolite accumulation. Genomic plot was used to estimate the ratio of specific-to-nondisplaceable uptake ( BPND) without using a receptor blocking drug. Both tracers quantified mGluR5; however [11C]SP203, like [18F]SP203, had radiometabolite accumulation in brain, as evidenced by increased distribution volume ( VT) over the scan period. Absolute VT values were ∼30% lower for 11C-labeled compared with 18F-labeled radioligands, likely caused by the lower specific activities (and high receptor occupancies) of the 11C radioligands. The genomic plot indicated ∼60% specific binding in cerebellum, which makes it inappropriate as a reference region. Whole-body scans performed in healthy subjects demonstrated a low radiation burden typical for 11C-ligands. Thus, the evidence suggests that [11C]FPEB is superior to [11C]SP203. If prepared in higher specific activity, [11C]FPEB would presumably be as effective as [18F]FPEB for quantifying mGluR5 in human brain.

Keywords: FPEB; PET imaging; SP203; genomic plot; mGluR5.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Carbon Radioisotopes
  • Female
  • Healthy Volunteers
  • Humans
  • Image Processing, Computer-Assisted
  • Ligands
  • Male
  • Models, Biological
  • Nitriles / blood
  • Nitriles / pharmacokinetics*
  • Positron-Emission Tomography / methods*
  • Pyridines / blood
  • Pyridines / pharmacokinetics*
  • RNA, Messenger / genetics
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Receptor, Metabotropic Glutamate 5 / genetics
  • Receptor, Metabotropic Glutamate 5 / metabolism*
  • Thiazoles / blood
  • Thiazoles / pharmacokinetics*
  • Tissue Distribution
  • Whole Body Imaging

Substances

  • 3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile
  • 3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile
  • Carbon Radioisotopes
  • GRM5 protein, human
  • Ligands
  • Nitriles
  • Pyridines
  • RNA, Messenger
  • Radiopharmaceuticals
  • Receptor, Metabotropic Glutamate 5
  • Thiazoles